Fondaparinux to Prevent Thrombotic Complications and Graft Failure in Patients Undergoing Coronary Artery Bypass Graft Surgery: The Fonda CABG Study (Fonda CABG)

Fondaparinux Compared With Heparin to Prevent Thrombotic Complications and Graft Failure in Patients Undergoing Coronary Artery Bypass Graft Surgery

(i) Main Research Question(s): What is the effect of fondaparinux on coronary graft patency, heart attack, stroke, and death in patients who have undergone coronary artery bypass grafting (CABG)? To reliably answer this question requires a large randomised trial. We propose a pilot study to demonstrate the feasibility of recruiting patients into this study and of performing CT angiograms to measure graft patency at 30 days.

(ii) Why is this research important? Coronary artery bypass surgery has made a very important contribution to improving the health and survival of patients with advanced coronary artery disease but still has many problems. One in 10 patients experiences a heart attack at the time of surgery, 1 in 20 experiences a heart attack, stroke, or death during hospitalization, and 1 in 4 patients has at least 1 blocked graft within 1 year of surgery. Fondaparinux, a relatively new anticoagulant drug, has been shown to significantly reduce cardiovascular events and death in patients who have suffered a recent heart attack. Compared to established anticoagulant therapies for acute myocardial infarction, fondaparinux has been shown to be more effective with similar or lower risks of bleeding.

Fondaparinux, unlike the most commonly used anticoagulants, does not cause Heparin Induced Thrombocytopenia (HIT), a rare condition with extremely high morbidity and mortality.

This drug has never been studied in CABG patients. Our pilot study will provide key information about feasibility that will help us to design and perform a large definitive study in the future.

(iii) What is being studied? We will be looking at blood flow in bypass grafts, heart attack, stroke, venous thromboembolism and death. For safety we will be looking at bleeding, transfusion, and need for further surgery because of bleeding. We will also perform laboratory tests for HIT antibodies as their levels are prognostic for the development of HIT and are also related to morbidity and mortality. The incidence of actual HIT cases will also be recorded.

Study Overview

• Status: Unknown
• Conditions: Coronary Bypass Graft Failure/Occlusion
• Intervention / Treatment: Drug: Fondaparinux

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Hamilton General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age at least 18 years
• undergoing first ever multivessel CABG-only surgery with at least 2 free grafts (e.g. Radial artery, saphenous vein, free internal mammary artery)
• undergoing CABG with cardiopulmonary bypass

Exclusion Criteria:

• clear indication for anticoagulation (e.g. prosthetic heart valve replacement, recurrent DVT)
• allergy or intolerance of fondaparinux or unfractionated heparin
• renal failure or other contraindication for coronary artery graft CT angiogram
• inability to provide informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Graft patency	28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Myocardial infarction	In-hospital
Stroke	In-hospital
Death	In-hospital
Bleeding events	In-hospital, 28 days
Transfusion requirements	In-hospital
Re-operation	In-hospital

Collaborators and Investigators

• Sponsor: Hamilton Health Sciences Corporation
• Collaborators: GlaxoSmithKline
• Investigators: Principal Investigator: Jack CJ Sun, MD, McMaster University; Study Director: John W Eikelboom, MD,MSc, McMaster University; Study Chair: Kevin HT Teoh, MD,MSc, McMaster University; Study Chair: Salim Yusuf, MD,DPhil, McMaster University

Publications and helpful links

General Publications

• Warkentin TE, Sheppard JI, Sun JC, Jung H, Eikelboom JW. Anti-PF4/heparin antibodies and venous graft occlusion in postcoronary artery bypass surgery patients randomized to postoperative unfractionated heparin or fondaparinux thromboprophylaxis. J Thromb Haemost. 2013 Feb;11(2):253-60. doi: 10.1111/jth.12098.

Study record dates

Study Registration Dates

• First Submitted: May 16, 2007
• First Submitted That Met QC Criteria: May 16, 2007
• First Posted (Estimate): May 17, 2007

Study Record Updates

• Last Update Posted (Estimate): May 28, 2007
• Last Update Submitted That Met QC Criteria: May 25, 2007
• Last Verified: May 1, 2007

More Information

Terms related to this study

• Keywords: Coronary artery bypass surgery, fondaparinux, graft patency, graft occlusion, graft failure, anticoagulation
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Fondaparinux; PENTA
• Other Study ID Numbers: 06-361